NIH Backs Search for Unique Sickle Cell Treatment

The National Institutes of Health (NIH) awarded Dr. Betty Pace and the Sickle Cell Disease Research Center (SCDRC) an award totaling $1.5 million over four years. The funding allows the SCDRC to explore the exciting possibilities that fetal hemoglobin (HbF) can offer to patients who suffer from the pain and agony of sickle cell disease.

Pace, who directs the SCDRC, said research shows that HbF—a protein in blood cells—prevents the ability of sickle hemoglobin to make red cells stiff or curved (sickle shaped) to avert symptoms of the disease. Hemoglobin is responsible for delivering oxygen to the tissues.

People who suffer the effects of sickle cell disease can face debilitating strokes and pain in their extremities because sickle red cells tend to block very small capillaries such as those in the hands and feet.

“Normally, fetal hemoglobin levels are high in the womb,” Pace said. “After birth, the level decreases and then normal Hemoglobin A, or adult hemoglobin, is produced. But some people only make fetal hemoglobin, and they’re fine—no symptoms. Our research effort to increase fetal hemoglobin in sickle cell disease takes advantage of this fact. We’re interested in studying two aspects of fetal hemoglobin.”

First, Pace’s lab will do an incredibly detailed search for drugs that increase levels of HbF. Hydroxyurea, an anti-cancer drug already on the market increases HbF but can present side-effects that include nausea, vomiting and unknown risk for cancer long-term. Pace is searching for other existing drugs that increase HbF without such negative side effects. Her lab is collaborating with Dr. Kenneth Peterson at the University of Kansas, who will test more than 100,000 drugs to learn which ones increase HbF.

The other prong of the research, funded by NIH, teams Pace with Dr. Michael Story, associate professor at UT Southwestern Medical Center. Pace and Story are studying the HbF gene itself.

“They will test all of the genes in the human genome at one time using microarray techniques—up to 42,000 genes on a chip—and we will perform the molecular studies at our research center. We’re interested in identifying approaches to control expression of the HbF gene,” said Pace.

Other research in Pace’s lab is focused on a genetic cure for sickle cell disease. Pace plans to take small pieces of DNA and use these custom-tailored “slices of life,” so to speak, to correct the sickle cell genes. Genes, are made up of “A, T, G and C” base pairs – or building blocks, that control almost everything in our bodies. A single mutation – where a genetic “A” has been switched to a “T” – causes the sickle cell mutation. Pace hopes to essentially patch the error with a new piece of DNA.

Pace, who was interviewed for the November issue of Ebony magazine, said her interest in treating this disease goes all the way back to her childhood. Children in a family close to hers suffered from the disease, and Pace had to endure the pain of losing a childhood friend to the condition. Given a variety of disciplines to enter into after medical school, she reached back into her past for the inspiration to uncover future treatments and cures for sickle cell disease.

“There are other treatments out there, even a cure,” Pace said. “More than 250 children have been cured by bone marrow transplants, but less than 10 percent of children have suitable donors. We’re looking for universal cures. Researchers in this field feel confident that within the next decade we’ll have a universal cure for sickle cell disease that doesn’t require a donor.”

Pace, a frequently invited speaker, recently spoke at the 16th annual Hemoglobin Switching Conference in Monterrey, Calif. Experts were invited from around the world to present the latest advances in the hemoglobin field.